<p>Cutaneous head and neck malignancies can display a phenomenon of tumour spread, called perineural spread (PNS), associated with reduced overall- and disease-specific survival. Benign conditions can present in a similar manner, of which viral neuritis is commonest. This can create diagnostic difficulties for clinicians who may perform thorough oncologic work up, including biopsy of the affected nerve(s). This study aims to educate readers about the overlap between PNS and viral neuritis and provides recommendations for investigation for patients with this overlap. Retrospective analysis of clinical, radiological, and histopathological findings of patients with pain, paraesthesia, dysesthesia, numbness, or paralysis in head and neck dermatome(s) who underwent work-up for suspected PNS from 2000 to 2022. Eligible patients did not have PNS on histology (where biopsy was performed) and were assumed to have viral neuritis based on the presence of inflammatory infiltration on PD-L1 staining. Additionally, eligible patients had surveillance imaging for at least 24-months or until nerve enhancement or symptoms resolved. Patient MRIs were reviewed by a senior radiologist (MG). Available surgical specimens were re-examined by a senior pathologist (DL). Twenty patients were selected, 15 were eligible. Viral neuritis more commonly presented with acute, rather than gradual, onset symptoms. Benign neuritis more commonly showed smooth enhancement and resolved within 18 months. Radiological and clinical exceptions are highlighted. Three nerve biopsies were re-examined and did not show malignancy. This study informs audiences about differential diagnoses of enhancing nerves on MRI and showcases the overlap between PNS and viral neuritis. Further studies are required to further improve understanding of the differences between PNS and viral neuritis.</p>